The regulation of free fatty acids (FFA) and ketone body metabolism will be studied in the intact fasted and streptozotocin-diabetic rat. Blood concentrations of FFA will be increased in fasted rats using two methods: infusion of a triglyceride emulsion and heparin, and infusion of an oleic acid emulsion stabilized with albumin. These two methods, which give quite different results, especially in the stimulation of insulin secretion, will be compared to determine reasons for the discrepancies. This will involve comparing their rate of removal from the blood using radioactive tracers and their effects on insulin and glucagon secretion. Blood concentrations of FFA will be increased in the diabetic rats by infusing either emulsions of oleic acid or triglycerides with heparin. During infusion, blood concentrations of FFA, ketone bodies, insulin and glucagon will be determined. Appropriate radioactive tracers will also be used during the infusion to measure the rates at which endogenous FFA appear and disappear from the blood. The extrahepatic metabolism of acetoacetate and hydroxybutyrate will be studied in fasted or diabetic rats which have been depancreatized and functionally hepatectomized. During the infusion of ketone bodies, the rates of extrahepatic production, utilization and interconversion of each of the two ketone bodies, will be measured using radioactive tracters. The effect of insulin on these rates will be determined.